Monday, 12 September 2011

Maybe you’re tired of grotting away at the lab bench. Or
finding it hard to get a tenured job. Perhaps your last paper was rejected and
you haven’t the spirit to fight back. Do not despair. There is an alternative. The
media are always on the look-out for a scientist who will fearlessly speak out
and generate newsworthy stories. You can gain kudos as an expert, even if if
you haven't got much of a track record in the subject, by following a few simple rules.

Rule #1. Establish your credentials. You need to have lots of letters after your
name. It doesn’t really matter what they mean, so long as they sound impressive.
It’s also good to be a fellow of some kind of Royal Society. Some of these are
rather snooty and appoint fellows by an exclusive election process, but it’s a
little known fact that others require little more than a minimal indication of
academic standing and will admit you to the fellowship provided you fill in a
form and agree to pay an annual subscription. So sign up as a Fellow of the Royal Society of Medicine, and keep good company with a range of naturopaths, homeopaths and chiropracters
who have discovered this easy route to eminence. The really nice thing is that
even academics can be hoodwinked by this one.

Rule #2. Find a controversial topic. This is key. You have to be
willing to take a definite position on something that people have strong views
about. A scare story is good - we’ve all been doing X for years but it could
damage us. Finding someone to blame is also good - people who do Y are
feckless. And the buzz word of the decade is neuroscience, so if you can work
that in, success is guaranteed. If you're short of ideas, the list of the right might help inspire you. A recent article in the Biologist hits the spot with “The biological
effects of day care”, managing to get us worried about an everyday activity,
blame working mothers, and get in a neuro message all at once. It's even spiced up with a bit of conspiracy theory: experts know that day care is bad for
children’s brains but nobody is allowed to speak out because it is too
politically sensitive. This presses so many buttons that few journalists could
resist the story.

Rule #3. Specify a causal chain. As we shall see when it comes to
assembling evidence, it is particularly useful to have a causal chain with
several steps. For instance:

The point here is that if you can usually find at least some
studies that provide evidence for bits of the causal chain. Although it may be
inconvenient if, as in this case, studies looking for a link between A and D
fail to come up with clear evidence (Lucas-Thompson et al, 2010), you can rely on two things: first, few
readers will be familiar with the research literature, so they will only know
as much as you tell them. And second, step C, brain abnormality, is highly
salient and once you start talking about that, it will distract attention from
the other levels of description.

Rule #4. Avoid rigorous peer review. You don’t want to have your views
critiqued by someone who knows the literature, or checks your sources. Writing books is a safe bet for avoiding pre-publication scientific critique.
As far as journals go, the Biologist is ideal. This publication
for the members of the Society of Biology claims to be peer-reviewed, but, as we shall see, the review process is far from rigorous.

Rule #5. Assemble supportive evidence. Note, it is important not
to present all relevant studies, just those with findings that can be fitted
into the causal chain.

The author of the paper in question, Dr Aric Sigman, presents us with so much positive evidence that he manages to give the impression that the whole casual chain has been validated. He starts by
mentioning studies that investigated the link between A and B and find that
salivary cortisol is increased in the afternoons in children attending day care. This is a product of the hypothalamo-pituitary-adrenal (HPA) axis, which is elevated in response to stress.
This result is well-established, both from studies comparing groups of children who do
and don’t attend day care, and from comparing the same children on days when
they stay at home or go to day care. This is a potentially concerning finding, if it can
be shown that there are consequences for children’s learning and behaviour.
As Sigman notes “Of central concern is that the routine stress experienced at
day care could cause permanent changes in the child’s neuroendocrine networks,
with long-term consequences for their mental and physical health as adults.”
(p. 30). The article that he cites does discuss this
issue, but notes the complexity of causal relationships and cautions against assuming that the cortisol elevation is harmful.
In fact the authors draw attention to an animal study suggesting a very different conclusion:

“As
in the work on cortisol responses to fullday child care, these separations in
squirrel monkey infants produced marked and repeated activations of the HPA
axis. However, followed into the late juvenile and early adult age, animals
exposed to this form of early life stress were found to be less fearful, to produce lower
rather than higher cortisol responses to stressors, and to show more optimal development of prefrontal
regulatory brain circuits; consistent with these findings, they also performed better on tests of executive
functioning. Thus, at least for this animal model, repeated separation stress early in life fostered a form of resilience.”
Gunnar et al (2010) (my emphasis)

Sigman
avoids mentioning any of this and turns instead to look at the links between
cortisol levels and ill health, starting with studies that show a link
between cortisol and cardiovascular disease. He does not explain that these
were done on people aged over 65 years, but rather implants in people’s minds
the notion that this is relevant for his arguments about daycare in toddlers. Next comes the serious stuff: research
linking elevated cortisol to the brain. We are told that “Cortisol is
considered neurotoxic and has a global impact on cerebral size (e.g. McEwen
2007; Sheline 2003).” (p. 29). Again, we are left with the distinct impression
that children who attend day care will have small brains, but to find out what
actually is meant here we need to read the cited articles. When we do, we find
that McEwen (2007) is a thorough research review of the physiologyand neurobiology of stress and
adaptation that nowhere mentions the terms ‘neurotoxic’, ‘global’ or
‘cerebral size’. Rather, in this article McEwen develops a complex theory that
considers both positive and negative impact of stress. It actually has a
section subtitled “Protection and damage: the two sides of the response to
stressors” which discusses animal studies demonstrating how elevated cortisol
can either improve or interfere with brain function, depending on context. Neurotoxicity does feature in the other
article, by Sheline (2003), but this is concerned with mood disorders in
adults, and discusses effects of hypercortisolemia, a condition where there
is chronic elevation of cortisol, rather than a temporary increase at specific
times of day. Subsequent citations are to papers that considered the role of
cortisol in psychiatric disorders such as anxiety and depression: note that now
the evidence is focused on a link between cortisol and adult psychiatric
disorders in the opposite direction (from D to B), yet it is presented in the
context of discussing consequences of high cortisol in children who attended
day care. Sigman further states: “a higher cortisol awakening curve may be a
biological marker for an underlying disposition towards developing depressive
and anxiety disorders” (p. 30), even though the studies of toddlers attending day care show a cortisol response that develops through the day, rather than a chronically raised level: see Vermeer and van IJzendoorn (2006) for a well-balanced discussion of such evidence.

It would be tedious to wade through every cited article, but
it’s worth considering just one more example. We are told “In human grey
matter, the quality of a mother’s care in early childhood is thought to alter
the size of the hippocampus (Buss et al, 2007)” (p. 30). Erm no. Buss et al clearly
stated there were no differences in left or right hippocampal volume between
those categorised as having high or low maternal care. What they did find was a
complicated interaction between birth weight, gender and maternal care, such
that birth weight predicted hippocampal volume only in female subjects
reporting low maternal care. But even this limited result doesn’t support
Sigman’s case. We are talking about ‘low maternal care’, not ‘attendance at
daycare’. And guess what? When we look at ‘low maternal care’ we find it measured
from a self-report questionnaire, where low care is partly identified in terms
of maternal overprotection. Those
categorised this way were more likely to have endorsed items describing their mother in such terms
as:

Tended to baby me

Tried to make me feel
dependent on her

Felt I could not look
after myself unless she was around

Was
overprotective of me

I’m
not an expert in the neurobiology of stress. I can track down articles that
appear to have been cited by Sigman (the reference list is behind a paywall)
and see where he's given a misleading account, but what I don’t know is how
much relevant literature has been omitted. This, of course, is what the celebrity scientist can rely on: there's only a handful of people who both have the
expertise in the area, and are obsessive enough to trawl through your writing
(if they can access it) and challenge any misleading statements.

Rule #6. Anticipate criticism but don't let it worry you. People who actually do research in the area you are reviewing may get irritated, but most scientists in the field wouldn’t bother on the grounds that they don't know who you are, and aren’t interested in pursuing academic debates outside the
domain of mainstream journals. The worst you may get is a few nerdy bloggers such as Gimpy or Mind Hacks criticising you for lack
of scholarship, sensationalism and cherrypicking of evidence. Or, if you're really unlucky, you might be up against Ben Goldacre on Newsnight. But meanwhile, your purpose as celebrity
scientist has been achieved: your views are all over the media.

Thursday, 1 September 2011

If a child has language problems, when would be the best age
to intervene? At 18 months of age, when they’re just at the outset of learning
language, or at five years, when they’re in school? Most people would say this
is a no-brainer, with early intervention being preferred on two counts:

There
are all kinds of secondary consequences of language difficulties: effects
on self-esteem, educational outcomes and social interactions. Potentially,
early intervention can avoid these.

It
is easier to influence the course of development while the brain is still
plastic. An analogy can be made with vision, where it is well-recognised
that amblyopia (or "lazy eye") needs to be corrected early in
life, because otherwise visual pathways in the brain do not develop
normally, and the potential for good vision in the lazy eye is lost.

Currently, interest by policy-makers in early intervention
has focussed mainly on children’s social and emotional outcomes, with a report by MP Graham Allen emphasising
the benefits, not just for children’s outcomes, but also in economic terms. The
argument is that by preventing problems from developing, we have the potential
to save millions of pounds that would otherwise be spent in dealing with
problems that manifest later in childhood.

The Allen report does not say much about children’s language
development, but similar arguments are often made, and in some areas of the
country, speech and language therapy services put most of their resources into
intervention with preschoolers.

There is, however, a problem with early intervention that is
easily overlooked, but which is well-documented in the case of children’s
language problems. This is the phenomenon of the "late bloomer". Quite simply,
the earlier you identify children’s language difficulties, the higher the
proportion of cases will prove to be "false positives" who spontaneously move
into the normal range without any intervention. We’ve known about this
phenomenon for many years: For instance, a study conducted by Fischel et al in 1989 followed 26
two-year-olds recruited because their parents reported that they understood
complete sentences but could say only a few words.
Five months after initial assessment, one third still had problems, one third
had made some improvement, and one third were in the normal range. Another
study by Thal et al in 1991 followed ten children who scored in the bottom 10% for expressive
vocabulary at the age of 18 to 29 months.
One year after initial assessment, six had caught up, whereas the remaining
four still had delayed language. These early small-scale studies have since
been confirmed by much larger population-based studies in the Netherlands and Australia.

The late-bloomer phenomenon was neatly demonstrated in a study just published in the British Medical Journal by an Australian team
headed by paediatrician Prof Melissa Wake and speech pathologist Prof Sheena Reilly. They
recruited children from a large population-based study, where parents were
asked to complete a Sure Start vocabulary screening measure when their child
was 18 months of age, as well as a child behaviour checklist. Around 20 per
cent of children were reported as having no or very limited spoken words. 301
of these children were randomly allocated to intervention or control groups.
The intervention, "Let's Learn Language", was based on a widely-used approach where parents are trained
to adopt strategies to enhance communicative interactions with their child. The
children were then given a detailed assessment at two years of age, and again
at three years. Results were striking: there were no hints of any difference
between children in the intervention group and control group on any language or
behavioural measures, either at 2 years or at 3 years.

The study authors noted various strengths and weaknesses of
their study. Among these they discussed the possibility that the intensity of
the intervention (six weekly sessions, each lasting 2 hours) may not have been
enough. But they went on to note that “the normal mean language and
vocabulary scores achieved by both intervention and control children by age 3
years suggest that natural resolution, rather than our intervention’s intensity
being too low, explains the null findings.”

They then point out the sobering conclusion to be drawn:
quite simply, if you intervene with children who are likely to improve
spontaneously, there will considerable waste of government’s and families’
resources.

Does this mean we should give up on early intervention? No.
But it does mean that we need to target such intervention much more carefully.
At present, one of the big questions for those of us investigating late talkers
is to find characteristics that will allow us to identify those children who won’t make spontaneous progress. This has
proved to be surprisingly difficult.

Another important message applies to intervention studies
more generally. If you provide an intervention for a condition that
spontaneously improves, it is easy to become convinced that you’ve been
effective. Parents were very positive about the intervention program. There was
remarkably good attendance, and when asked to rate specific features of the
program and its effects, around three quarters of the parents gave positive
responses. This may explain why both parents and professionals find it hard to
believe such interventions have no impact: they do see improvement. Only if you
do a properly controlled trial will the lack of effect become apparent, not
because treated children don’t improve, but rather because the control group
gets better as well.